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Abstract #1026

Creatine Deficiency, Uptake and Breakdown Studied in Brain and Muscle of Arginine:Glycine Amidinotransferase Deficient Mice

Christine Nabuurs1, Martijn Romeijn1, Andor Veltien1, Hermien Kan1, Dirk Isbrandt2, Arend Heerschap1

1Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; 2Institute for signal transmission, Hamburg, Germany

Arginine:glycine amidinotransfererase is an essential step in the biosynthesis of creatine. Inborn errors of genes for this enzyme lead to creatine deficiency syndromes, which can be treated by oral Cr intake. However, the rates of Cr uptake in different tissue types have not been assessed. In this study we determined total Cr uptake and breakdown in muscle and brain of mutant mice with AGAT deficiency by means of a longitudinal 1H MRS study. Muscle tissue demonstrated remarkably fast uptake, already after 1 day the levels of tCr were comparable to that of wildtypes. In contrast, uptake in brain was much slower reaching normal levels at ~20 days of treatment. These results suggest that the blood-brain-barrier significantly delays uptake of Cr in brain.